CA1183533A - 2(1h)-pyridinone derivatives, their preparation and pharmaceutical compositions containing them - Google Patents

2(1h)-pyridinone derivatives, their preparation and pharmaceutical compositions containing them

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Publication number
CA1183533A
CA1183533A CA000372050A CA372050A CA1183533A CA 1183533 A CA1183533 A CA 1183533A CA 000372050 A CA000372050 A CA 000372050A CA 372050 A CA372050 A CA 372050A CA 1183533 A CA1183533 A CA 1183533A
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Canada
Prior art keywords
phenyl
formula
compound
carbon atoms
acceptable salt
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
CA000372050A
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French (fr)
Inventor
Gerhard Bormann
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Sandoz AG
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Sandoz AG
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Publication of CA1183533A publication Critical patent/CA1183533A/en
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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72Nitrogen atoms
    • C07D213/73Unsubstituted amino or imino radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81Amides; Imides
    • C07D213/82Amides; Imides in position 3

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

A b s t r a c t The compounds of formula I, I

wherein R1 and R2 independently are hydrogen, alkyl or optionally substituted monocyclic aryl with the provisos that a) at least one of R1 and R2 is aryl and b) when R2 is hydrogen, then R1 is other than 2-, 3- or 4-pyridinyl unsub-stituted or substituted by one or two lower alkyl groups.
are useful as cardiotonic agents.

Description

Case 100~5374 _ .
2 (lH)-PYRIDI~OM.E DERIVP.TIVES, THEIR PREPARP~TION A2~D
PHAR~lAC~lJ'rICAL COMPOSITIONS CONTAINING THEM
, . .. _ ._ . , The prPsent invention relates to 2(lH)-pyridone derivatives, their preparation and pharmace~tical compositions containing them.

In particular, the invention provides compounds of formula I, Rl~NH2 R2~}1.?, wherein Rl and R2 independently are hydrogen, alkyl or option-10 . ally substituted monocyclic aryl wlth the provisos that a) at ].east one of Rl and R2 is aryl andb) when R2 is hydrogen, then Rl is other than 2-, 3-- or 4-pyridinyl, un-substituted or substituted by one or t~o lower alkyl groups, hereinafter referred to as "the compounds of the invention".

It is to be appreciated that for the sake of simplicity the compounds of the inventions are defined with reference to the tautomeric form of formula I. However, the invention extends to all tautomeric forms of ~he compounds, e.g. the iminol form.

As used herein, the term "monocyclic aryl"
indicates a radical bonded through an unfused aromatic ring. The ring may be carbocyclic, such as phenyl, or heterocyclic contalning up to 3 h teroato~s. As indicated, the raclical may be substituted or unsubstituted.

~ ~3~33 ~ 3 - 100-5374 In accordance with the invention, there are especially provided compounds of formula Ia, 1 ~ ~ ~ 2 Ia R2a 1 0 wherein Rla and R2a independently are i) hydrogen or alkyl of 1 to 4 carbon atoms, ii) phenyl, phenyl monosubstituted by di-alkylamino of independently 1 to 4 carbon atoms in each alkyl moiety or phenyl mono-or independently disubstituted by alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halogen o atomic number of from 9 to 35 or ~ iiij pyrrolyl, furanyl, thienyl, thiazolyl, imidazolyl~ pyrazolyl, pyridinyl, pyri-midinyl, pyridazinyl or pyrazinyl with the pro~isos that a ) at least one of Rl and R2a has the above signi-ficance ii) or iii) and b ) when R~ is hydrogen, then Rl is other than 2-, 3- or 4-pyridinyl.

~L835~3 ~ 0-537~

Alkyl of 1 to 4 carbon atoms and alkoxy of 1 to ~ carbon atoms preferably are of 1 or 2, especially 1 carbon atom. Halogen preferably is chlorine or bromine, especially chlorine. In dialkylamino the t~70 alkyl moieties preferably are identical. Pyrrolyl preferably is 3-pyrrolyl. Furanyl preferably is
3 furanyl. Thienyl preferably is 3-thienyl. Thiazolyl preferably is 4 -thiazolyl. Imidazolyl preferably is
4 -imidazolyl. Pyrazolyl prefer~bly is 3-pyrazolyl.
Pyridinyl preferably is 2- or 4-, especially 4-pyri-dinyl. Pyrimidinyl preferably is 4-pyrimidinyl.
Pyridazinyl preferably is 4-pyridazinyl. Pyrazinyl preferably is 2-pyrazinyl.

Rl preferably is alkyl or has the above sig-nificance ii) or iii). Rl especially has significanceii). R2a preferab]y has the above significance i~, it especially is ~et:hyl. Significance i) preferably is alkyl. Significance ii) preferably is unsubstituted or monosubstituted phenyl. When ~t is monosubstituted phenyl, the substituent preferably is in the m- or p-, especially in the p-position. h~hen it is disubstituted phenyl, the su~stituents preferably are in the m-and p-posltions.They preferably are identical. Pre'erred substituents of the phenyl group are alkoxy and halogen, especially alkoxy. Slgnificance iii) prefer-ably is pyrrolyl, furanyl, th~enyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl, especially furanyl, pyridinyl, pyrimidinyl or pyrazlnyl, ~3~33 ~ 5 ~ 100-537 especially pyrimidinyl or pyridinyl, especially pyrimidinyl. Preferably one of Rla and R2a has signi-ficance i).

In one group of compounds of formula Ia Rl and R2 are other than pyridinyl. In a subgroup they have a significance other than significance iii).

A preferred group of compounds of formula Ia is the compounds of formula Iaa, aa ~ Iaa H3~1 0 wherein Rala has siginificance ii) or iii) indicated above.

In one group of compounds of formula Iaa Rlaa is other than pyridinyl. In a subgroup Rlaa has slgnificance li) indicated above.

. . . .. . . . . .. . . . . . . . . ..
A further group of compounds of formula Ia is the compounds of_formula Ipa 1 ~ H2 Ipa RP o H

3~3~

wherein a is i) phenyl, phenyl monosubstituted by dialkyl-amino of independently 1 to 4 carbon atoms in each alkyl moiety or phenyl mono- or indepen ~dently disubstituted by alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halogen of atomic number of from 9 to 35, or ii) pyrrolyl, furanyl, thienyl 7 pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl and Rpa is alkyl of 1 to ~ carbon atoms.

A further group of compounds of formula Ia is the compounds of formula Ipb, ~pb ~ H2 ' Ipb RP~/

wherein
5 RPlb i5 hydrogen or alkyl of 1 to 4 carbon atoms and R2b has the significance indicated above for RPa .

A further group of compounds of formula Ia is the compounds of formula Ipc, 3~3;~

1 ~H2 ll I Ipc H

wherein RlPC with the exception of ~yridinyl. has the significance indicatea above for RP

In accordance with the invention, a compoun~l of the invention may be obtained by a process comprisins aminating a corresponding compound of formula II, 1 ~ X
R2 ~ ~0 wherein Rl and ~2 are as defined above and Rx is a group capable of conversion to a primary amino group.
-The amination process may be effected inconventional manner for the production of analogous 3-amino~2~lH)-pyridinone derivatives. Rx may be a conventional radical used for conversion to a primary amino group, such as nitro and especially carbamoylO For example, when Rx is carbamoyl, the ~3~33 - ~ - 100 5374 reaction conditions of a Hofmann degradation may be used. The reaction preferably is effected under strong alkaline conditions, e~g. in the presence of an alkali metal hydroxide and bromine. P~ferably water is used as a solvent. Suitable reaction ~em-peratures may be from about 50 to about 100C, conveniently about 100C.

The compounds of formula I may be isolated from the reaction mixture and purified in a manner ana-logous to kno~m methods.

The compounds of the invention may exist in free base form or in salt form. Pree base forms may be converted into salt forms in conventional ~anner and Yice-versa. Suitable acids for acid addition salt formation include hydrochloric, malonic, p-toluene-sulfonic and methanesulfonic acid. Suitable bases for anionic salt formation include sodium and potassium hydroxide~

The starting materials may be obtained in known manner.

. . .
In particular, a.compound of formula II , wherein R is carbamoyl, may e.g. be obtained by partial hydrolysis of a corresponding compound of formula III, lWC~
~2 1 ~ III
H

wherein Rl and P~2 are as defined above, e.g. wi~h sulfuric or phosphoric acid.

A compound of formula III may e.g. be obtained by reacting a co:rresponding compound of formula IV, R

1~ NAlk2 ~ IV

wherein Rl and R2 are as defined above and Alk is lower alkyl, peferably methyl, with cyanacetamide.
The reaction may e.g. be effected in the presence of acetic acid, in which case a:.compound oi formula II may be directly obtained~

~3~33 - 10 ~ 100-5374 A ~ompound of formula IV may e.g. be obtained by reacting a corresponding compound of ~ormula V, Rl~
V
R2/ ~0 wherein Rl and R2 are as defined above, with an~,N-di(lo~er)alkyl formamide di(lower~alkyl acetal, prefer-ably N,~-dimethylformamide dimethyl or diethyl acetal.

Insofar as the preparation of any particular starting material is not particularly described, this may be effected in conventional manner or in analogous manner to that desCribed herein.

In the following Examples all temperatures are in degrees Centigrade and are uncorrec~ed.

~3~:i33 3-Amino-6-methyl-S-phenyl-2(1H
pyridinone 2.1 ml of bromine are addea dropwise at 0 to a stirred solution of B.4 g of sodium hydroxide in 125 ml of water. 7~3 ~ of 1,2-dihydro-~-methy-1-2~
oxo-S-phenyl~nicotinamide are then _ added and the mix~ure heated under stirring to 100 for 3 hours. After cooling to room temperature the resultant solution is carefully acidified with 6N hy-10 droc~loric acid and stirring continued for 30 minutes.
The resulting precipitate is filtered off under vacuum and recrystallized from methanol. The title compound is obtained (M.P. 260-263; M.P. of the mesylate salt form: 220-222 [dec.]).

The starting ma~erial i5 obtained as follows:

Benzylmethylketone and N,N-dimethYlformamide dimethyl acetal are heated to 80 for 5 hours. The so-obtained crude 4-dimethylamino-3-phenyl-3-buten-2-one is then reacted with cyanacetamide at koiling t~
perature in the presence of sodium ethoxide. The so-ohtained 1,2-dihydro-6-methyl-2-oxo-5-phenylpyridin-3-carbonitrile ~M.P. 290-294 - from methanolJ is then partially hydrolysed with 90 ~ sulfuric acid at 100 to give 1,2 dihydxo-6-methyl-2-oxo-5-phenyl nicotinamide ~M.P.~ 300 - from dimethylformamide~.

35~31 - 12 - 103~5374 The following compounds of formula I may be obtained by reaction of the appropriate com.pound of formula II, wh-erein Rx is carbamoyl, in analogous manner to Example 1~

~33~:i33 , , _~
Example Rl R2 .
, . _ . ~___ 2 m-tolyl Me ~ 245-250 ~dec.
3 p-Cl-phenyl ~le ms 231-234 4 p-MeO phenyl Me b 256 260 m-,p diMeO-phenyl ~Ie b 218~220
6 phenyl Et b 192-194
7 o-tolyl Me .b 231-232
8 Me phenyl b 174-176
9 pyrimidin-4-yl H b 283-287 phenyl H ch 240-243 11 pyrazin-2-yl H b 262-264 12 I phenyl ?henyl b 296-299 13I furan-2-yl Me b 189 191 14¦ pyridin-2-yl ~phenyl b 239-242 15`I m-MeO-phenyl I Me b 244-245 16¦ pyridi.n~4-yl , Me I b 290-295 17j o-MeO-phenyl ' Me ¦ b 224-226 b = in free base form ch = in hydrochloride salt form ms = in mesylate salt form Et = ethyl Me = methyl dec. = decomposition MeO = methoxy ~3~i~3 - 14 - 1~0-5374 The compounds of the invention possess pharma-cological activity.

The compounds possess cardiotonic activity, as indicated by standard tests. For example, in the normotonic Numal anaesthetized dogl an increase in the contractile force of the left ventricle is observed upon intravenous administration of from about 0.02 to about 2 mg/kg.

The test method is as follows:
Dogs of either sex weighing from 10 to 15 kg are used. Numal in a dosis of 65 mg/kg i.v. is used as an anaesthetic. The animal is attached in supine position on the operation table. After the usual preparations have been effec~ed, a heparini7ed catheter is introduced along the Arteria carotis dextra into the left ventricle under radiological control and the transmission of the pressure is registered with a donor membrane (Gould Statham P 23 Gb). The increase in pressure as a function of time is computed and registered wi~h an HSE-physiodifferentiator. The pressure increase in the left ventricle is a measure of the contractile force of the heart. The magnitude of the pressure differential is indicated in mm ~g/sec A suitable body temperature (about 36 to 37C) i8 maintained constant. After a control period of about 40 minutes the test substance is injected into the Vena femoralis and it~ effect on the registered or computed parameters observed.

- 15 ~ 5374 The compounds are therefore indicated for use as cardiotonic agents, e.g. for ~he treatment of heart insuLficiency.

Preferred in this indlcatlon are the compounds cf Examples 1 and 4, especially the compound of Example 1.

~ n indicated daily dose is from about 10 ~g to about 500 mgt suitably administered,e g. orally, in divided dosages of from about 2.5 mg to about 250 mg of the compounds two ~o four times daily, or in re~ard form. An example of a daily dosage is from
10 to 100 mg.

The compoun~s may be administered in pharma-ceutically acceptable salt form, preferahly acid addition salt form. Such sal~ forms exhibit the same order of activity as the free forms and are readiiy prepared in conventional manner. The present invention also provides a pharmaceutical composition comprising a compound of the invention in free form or in phar-maceutically acceptable salt formr in associationwith a pharmaceutical carrier or dlluent. Such compositions may bP in the form of, for example, a solution or a tablet.

Claims (5)

CLAIMS:
1. A process for the production of a compound of formula Ia, Ia wherein R? and R? independently are i) hydrogen or alkyl of 1 to 4 carbon atoms, ii) phenyl, phenyl monosubstituted by di-alkylamino of independently l to 4 carbon atoms in each alkyl moiety or phenyl mono- or independently disubstituted by alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halogen of atomic number of from 9 to 35 or iii) pyrrolyl, furanyl, thienyl, thiazolyl, imidazolyl, pyrazolyl, pyrimidinyl, pyridazinyl or pyrazinyl with the proviso that at least one of R? and R? has the above signi-ficance ii) or iii) or a pharmaceutically acceptable salt form thereof, which comprises subjecting to a Hofmann degradation a corresponding compound of formula IIa, IIa wherein R1 and R2a are as defined in this claim and where indicated converting the resultant compound of formula Ia into a pharmaceutically acceptable salt form thereof.
2. A process according to claim 1 for the production of 3-amino-6-methyl-5-phenyl-2(1H)-pyri-dinone which comprises subjecting to a Hofmann de-gradation a corresponding compound of formula IIa wherein is phenyl and is methyl and where indicated converting the resultant compound into a pharmaceutically acceptable salt form thereof.
3. A process according to claim 1 which comprises adding 1,2-dihydro-6-methyl-2-oxo-5-phenyl-nico-tinamide to a solution of bromine in sodium hydroxide at 100°.
4. A compound of formula Ia, as defined in claim 1 or a pharmaceutically acceptable salt farm thereof, whenever produced by a process according to claim 1, or an obvious chemical equivalent thereof.
5. The compound of formula Ia defined in claim 2 or a pharmaceutically acceptable salt form thereof, whenever produced by a process according to claim 2, or an obvious chemical equivalent thereof.
CA000372050A 1980-03-03 1981-03-02 2(1h)-pyridinone derivatives, their preparation and pharmaceutical compositions containing them Expired CA1183533A (en)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
CH1669/80 1980-03-03
CH166980 1980-03-03
CH166880 1980-03-03
CH1668/80 1980-03-03
CH5717/80 1980-07-25
CH571780 1980-07-25
CH794780 1980-10-24
CH7947/80 1980-10-24

Publications (1)

Publication Number Publication Date
CA1183533A true CA1183533A (en) 1985-03-05

Family

ID=27428258

Family Applications (1)

Application Number Title Priority Date Filing Date
CA000372050A Expired CA1183533A (en) 1980-03-03 1981-03-02 2(1h)-pyridinone derivatives, their preparation and pharmaceutical compositions containing them

Country Status (16)

Country Link
CA (1) CA1183533A (en)
CH (1) CH652395A5 (en)
DE (1) DE3106460A1 (en)
DK (1) DK94481A (en)
ES (1) ES8301469A1 (en)
FI (1) FI810558L (en)
FR (1) FR2477148A1 (en)
GB (1) GB2070606B (en)
IL (1) IL62246A (en)
IT (1) IT1142458B (en)
NL (1) NL8100964A (en)
NZ (1) NZ196385A (en)
PT (1) PT72596B (en)
SE (1) SE8101336L (en)
WO (1) WO1981002575A1 (en)
YU (1) YU51581A (en)

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL65278A0 (en) * 1981-03-30 1982-05-31 Sterling Drug Inc 3-amino-5-(substituted)-2(1h)-pyridinones and corresponding 3-cyano compounds,their preparation and pharmaceutical compositions containing them
US4465686A (en) * 1981-09-08 1984-08-14 Sterling Drug Inc. 5-(Hydroxy- and/or amino-phenyl)-6-(lower-alkyl)-2-(1H)-pyridinones, their cardiotonic use and preparation
US4515797A (en) * 1981-09-08 1985-05-07 Sterling Drug Inc. 3-Amino-5-(hydroxy- and/or aminophenyl)-6-(lower-alkyl)-2(1H)-pyridinones and cardiotonic use thereof
US4593028A (en) * 1981-10-26 1986-06-03 William H. Rorer, Inc. 5-hetero aryl-substituted-2-pyridones useful as cardiotonic agents for treatment of congestive heart failure
US4432979A (en) * 1981-10-26 1984-02-21 William H. Rorer, Inc. Pyridone compounds
US4539321A (en) * 1981-10-26 1985-09-03 William H. Rorer, Inc. 5-Diaza-aryl-3-substituted pyridone compounds
US4514400A (en) * 1981-10-26 1985-04-30 William H. Rorer, Inc. Cardiotonic 5-heteroaryl-pyridone
FR2527206B1 (en) * 1982-05-18 1986-12-05 Sandoz Sa NOVEL 2 (1H) -PYRIDINONE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS MEDICAMENTS
AT384021B (en) * 1982-05-18 1987-09-25 Sandoz Ag Process for the preparation of novel 2(1H)-pyridinone derivatives and their salts
FR2529891A1 (en) * 1982-07-12 1984-01-13 Nativelle Sa Ets PYRIDYL-3 ALCOXY-5 PYRAZOLE DERIVATIVES, PREPARATION METHOD AND THERAPEUTIC APPLICATION
IT8367883A0 (en) * 1982-08-23 1983-08-22 Rorer Int Overseas CARDIOTONIC COMPOUNDS OF SUBSTITUTED BICYCLIC 2 PYRIDONE 5 HETEROARYL AND RELATED PHARMACEUTICAL COMPOSITIONS
IL69407A (en) * 1982-08-23 1987-10-20 Warner Lambert Co 2(1h)-pyridinones,their preparation and pharmaceutical compositions containing them
US4503061A (en) * 1983-07-22 1985-03-05 Warner-Lambert Company Substituted phenyl-pyridinones as cardiotonic agents
US4517192A (en) * 1983-01-31 1985-05-14 Sterling Drug Inc. 6-Alkyl-5-[4-(alkylsulfinyl or alkylsulfonyl)phenyl]-2(1H)-pyridinones and their use as cardiatonics
ES8600746A1 (en) * 1983-04-20 1985-10-16 Quimicos Y Farmaceuticos Abel Process for the preparation of 5-pyridyl-pyridine-2(1H)-ones.
US4568751A (en) * 1983-04-29 1986-02-04 Merrell Dow Pharmaceuticals Inc. 5-Acyl-2-(1H)-pyridinones
DE3406329A1 (en) * 1984-02-22 1985-08-22 Merck Patent Gmbh, 6100 Darmstadt PYRIDONE
DE3685840D1 (en) 1985-04-30 1992-08-06 Dresden Arzneimittel 3-CYAN-PYRIDINE, METHOD FOR THE PRODUCTION THEREOF AND THEIR PHARMACEUTICAL USE.
US4666913A (en) * 1985-11-22 1987-05-19 William H. Rorer, Inc. Hydroxy and aminothiazolyl-benzodiazinone compounds, cardiotonic compositions including the same, and their uses
US4785005A (en) * 1986-06-25 1988-11-15 Rorer Pharmaceutical Corporation 6-(6-alkylpyridone)-carbostyril compounds and their cardiotonic uses
US5254571A (en) * 1988-04-21 1993-10-19 Smith Kline & French Laboratories Ltd. Chemical compounds
GB8809481D0 (en) * 1988-04-21 1988-05-25 Smith Kline French Lab Chemical compounds
GB8923131D0 (en) * 1989-10-13 1989-11-29 Smith Kline French Lab Chemical compounds

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3355278A (en) * 1961-03-13 1967-11-28 Hooker Chemical Corp Herbicidal composition and method
NL6816241A (en) * 1967-12-01 1969-06-03
FR2050940A5 (en) * 1969-06-30 1971-04-02 Rhone Poulenc Sa
US3666765A (en) * 1969-10-27 1972-05-30 Union Carbide Corp Synthesis of 2-pyridones and derivatives thereof
US3721676A (en) * 1969-11-12 1973-03-20 Merck & Co Inc Certain 3-amino-2(1h)pyridones
BE758759A (en) * 1969-11-12 1971-05-10 Merck & Co Inc ANTI-INFLAMMATORY PYRIDONES
US4038396A (en) * 1975-02-24 1977-07-26 Merck & Co., Inc. Anti-inflammatory oxazole[4,5-b]pyridines
US4072746A (en) * 1975-10-14 1978-02-07 Sterling Drug Inc. 3-Amino-5-(pyridinyl)-2(1H)-pyridinones

Also Published As

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FR2477148A1 (en) 1981-09-04
NL8100964A (en) 1981-10-01
GB2070606A (en) 1981-09-09
IT8147920A0 (en) 1981-03-02
CH652395A5 (en) 1985-11-15
ES499971A0 (en) 1982-12-01
IL62246A0 (en) 1981-05-20
NZ196385A (en) 1983-12-16
YU51581A (en) 1983-12-31
GB2070606B (en) 1984-02-29
FI810558L (en) 1981-09-04
DK94481A (en) 1981-09-04
DE3106460A1 (en) 1982-01-28
IL62246A (en) 1984-09-30
SE8101336L (en) 1981-09-04
WO1981002575A1 (en) 1981-09-17
IT1142458B (en) 1986-10-08
PT72596B (en) 1982-07-13
FR2477148B1 (en) 1983-09-02
PT72596A (en) 1981-04-01
ES8301469A1 (en) 1982-12-01

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